Persistent Submicroscopic Plasmodium falciparum Parasitemia 72 Hours after Treatment with Artemether-Lumefantrine Predicts 42-Day Treatment Failure in Mali and Burkina Faso

Antimicrob Agents Chemother. 2021 Jul 16;65(8):e0087321. doi: 10.1128/AAC.00873-21. Epub 2021 Jul 16.

Abstract

A recent randomized controlled trial, the WANECAM (West African Network for Clinical Trials of Antimalarial Drugs) trial, conducted at seven centers in West Africa, found that artemether-lumefantrine, artesunate-amodiaquine, pyronaridine-artesunate, and dihydroartemisinin-piperaquine all displayed good efficacy. However, artemether-lumefantrine was associated with a shorter interval between clinical episodes than the other regimens. In a further comparison of these therapies, we identified cases of persisting submicroscopic parasitemia by quantitative PCR (qPCR) at 72 h posttreatment among WANECAM participants from 5 sites in Mali and Burkina Faso, and we compared treatment outcomes for this group to those with complete parasite clearance by 72 h. Among 552 evaluable patients, 17.7% had qPCR-detectable parasitemia at 72 h during their first treatment episode. This proportion varied among sites, reflecting differences in malaria transmission intensity, but did not differ among pooled drug treatment groups. However, patients who received artemether-lumefantrine and were qPCR positive at 72 h were significantly more likely to have microscopically detectable recurrent Plasmodium falciparum parasitemia by day 42 than those receiving other regimens and experienced, on average, a shorter interval before the next clinical episode. Haplotypes of pfcrt and pfmdr1 were also evaluated in persisting parasites. These data identify a possible threat to the parasitological efficacy of artemether-lumefantrine in West Africa, over a decade since it was first introduced on a large scale.

Keywords: Plasmodium falciparum; antimalarial agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials* / therapeutic use
  • Artemether / therapeutic use
  • Artemether, Lumefantrine Drug Combination
  • Burkina Faso
  • Drug Combinations
  • Ethanolamines / therapeutic use
  • Humans
  • Malaria, Falciparum* / drug therapy
  • Mali
  • Parasitemia / drug therapy
  • Plasmodium falciparum / genetics
  • Treatment Failure

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Drug Combinations
  • Ethanolamines
  • Artemether